Massachusetts General Hospital – Harvard Medical School
Circulating tumor cells (CTCs) are cells that are derived from a tumor, but are isolated from the blood of cancer patients. Only recently has technological advances permitted the isolation and characterization of these rare cells. CTCs offer a snapshot of the invasive cancer cells that give rise to metastatic lesions and an important model to study cancer and the stages of metastasis. The study of CTCs and the mechanisms of metastasis has the potential to catalyze the development of new treatments for breast cancer that more effectively target CTCs and prevent or suppress the development of metastasis.
To investigate breast cancer CTCs and metastasis, I have generated a mouse model of breast cancer metastasis and performed a screen to identify regulators of metastasis. From this screen I identified RPL15, an integral component of the ribosome, to investigate further. I have shown that increased levels of the RPL15 enhances breast cancer spread in mice. Additionally, in breast cancer patients, CTCs with high levels of ribosome proteins correlate with more aggressive disease. The goal of this proposal is to investigate how RPL15 affects metastasis, determine whether it also contributes to drug resistance to standard breast cancer therapy and determine whether targeting the function of ribosome proteins can specifically target these aggressive breast cancer CTCs. To achieve these goals, first, I will investigate how ribosome proteins increase metastasis. Then, I will use an FDA-approved protein translation inhibitor, omacetaxine, to test its ability to reverse drug resistance to commonly used breast cancer drugs. Finally, I will use innovative new microfluidic technology to increase the number of circulating tumor cells that can be isolated from a single patient allowing for more in depth studies of breast cancer metastasis and response to therapy.
Dr. Douglas Micalizzi received his medical degree from University of Colorado School of Medicine, completed internal medicine residency at Massachusetts General Hospital and medical oncology fellowship in the Dana Farber/Partners Oncology Fellowship Program. He is currently completing his post-doctoral research in the laboratory of Dr. Daniel Haber and Dr. Shyamala Maheswaran at the Massachusetts General Cancer Center. Dr. Micalizzi is also a breast medical oncologist at Massachusetts General Hospital specializing in cancer risk assessment and hereditary cancer syndromes.